The purpose of this study is to determine whether the early and continuous addition of bevacizumab for up to 30 months to the standard chemotherapy is more effective than the early and continuous addition of bevacizumab for up to 15 months.

Health related Quality of life (QoL) [ Time Frame: baseline, then every 12 weeks until progression, 31 months after start of treatment or if applicable 4 weeks after last dose of bevacizumab (whichever occurs later) ] [ Designated as safety issue: No ]

Patients receive bevacizumab iv followed by paclitaxel iv and carboplatin iv on day 1. Treatment repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab iv alone every 3 weeks for 16 cycles.

Biological: Bevacizumab

15 mg/kg, iv on day 1 every 3 weeks up to and including cycle 22

Drug: Paclitaxel

175 mg/m², iv on day 1 every 3 weeks for 6 cycles

Drug: Carboplatin

AUC 5, iv on day 1 every 3 weeks for 6 cycles

Other: specialized pathology review (Germany only)

before randomization

Experimental: Research Arm

Patients receive bevacizumab iv followed by paclitaxel iv and carboplatin iv on day 1. Treatment repeats every 3 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab iv alone every 3 weeks for 38 cycles.

Biological: Bevacizumab

15 mg/kg, iv on day 1 every 3 weeks up to and including cycle 44

Drug: Paclitaxel

175 mg/m², iv on day 1 every 3 weeks for 6 cycles

Drug: Carboplatin

AUC 5, iv on day 1 every 3 weeks for 6 cycles

Other: specialized pathology review (Germany only)

before randomization

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Signed written informed consent obtained prior to initiation of any study specific procedures and treatment as confirmation of the patients awareness and willingness to comply with the study requirements

Patients should have already undergone surgical debulking, by a surgeon experienced in the management of ovarian cancer, with the aim of maximal surgical cytoreduction according to the GCIG Conference Consensus Statement. There must be no planned surgical debulking prior to disease progression. Patients with stage III and IV disease in whom initial surgical debulking was not appropriate or possible will still be eligible providing

the patient has a histological diagnosis and

debulking surgery prior to disease progression is not foreseen

Patients must be able to commence cytotoxic chemotherapy within 8 weeks of cytoreductive surgery. The first dose of bevacizumab can be omitted in both arms if the investigator decides to start chemotherapy within 4 weeks of surgery.

Patients not receiving anticoagulant medication who have an INR ≤ 1.5 and an aPTT ≤ 1.5 x ULN

The use of full-dose oral or par-enteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to institution medical standard) and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of randomization.

Surgery (including open biopsy) within 4 weeks prior to anticipated first dose of bevacizumab (allowing for the fact that bevacizumab can be omitted from the first cycle of chemotherapy). It is strongly recommended that an interval of 7 days is left between the insertion of any central venous access devices (CVADs) and the onset of bevacizumab treatment.

Any planned surgery during the study treatment period plus 4 additional weeks to allow for bevacizumab clearance

Fertile woman of childbearing potential not willing to use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) for the study duration and at least 6 months afterwards

Pregnant or lactating women

Treatment with other investigational agents, or participation in another clinical trial testing a drug within the past 4 weeks before start of therapy concomitantly with this trial

Malignancies other than ovarian cancer within 5 years prior to randomization, except for adequately treated

carcinoma in situ of the cervix

and/or basal cell skin cancer

and/or non-melanomatous skin cancer

carcinoma in situ of the breast

and/or early endometrial carcinoma as specified below. Patients may have received previous adjuvant chemotherapy for other malignancies e.g. breast or colorectal carcinoma if diagnosed over 5 years ago with no evidence of subsequent recurrence.

Patients with synchronous primary endometrial carcinoma, or a past history of primary endometrial carcinoma, are excluded unless ALL of the following criteria for describing the endometrial carcinoma are met

Disease stage FIGO stage ≤ IA (tumour invades less than one half of the myometrium)

Known hypersensitivity to bevacizumab and its excipients, Chinese hamster ovary cell products or other recombinant human or humanised antibodies

Current or recent (within 10 days prior to randomization) chronic use of aspirin > 325 mg/day

Pre-existing sensory or motor neuropathy ≥ Grade 2

Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment-related complications

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01462890